Colony stimulating factors (hereinafter abbreviated as CSFs) are known as substances which stimulate proliferation and differentiation of hematopoietic stem cells, and they are categolized into following four items:
(1) factors which act on monocyte-macrophage lineage (M-CSFs), PA0 (2) factors which act on granulocyte-monocyte lineage (GM-CSFs), PA0 (3) factors which act on granulocyte lineage (G-CSFs), and PA0 (4) factors which act on multipotential stem cells (multi-CSFs)
Human M-CSFs are already isolated and purified, and their protein structures and genetic structure which participates production of M-CSFs or which encode amino acid sequence of M-CSFs have been described (cf: Japanese Unexamined Patent Application Gazette No. 64(1989)/22899).
Regarding tumoricidal activity of a CSF is described by A. Samson-Johannes et al (cf: Journal of Immunology, Vol. 141, 3680-3686, No. 10, Nov. 15, 1988).
It is also described that an hM-CSF may stimulate matured human monocyte-macrophage to produce various cytokines (cf: K. Motoyoshi et al, Experimental Hematology, Vol. 17, 68-71, 1989), that a human urinary M-CSF is clinically effective on granulocytopenia (cf: K. Motoyoshi et al, Experimental Hematology, Vol. 14, 1069-1075, 1986), and that a human urinary M-CSF is clinically effective in recovery of leukocyte and granulocyte numbers after bone marrow transplantation (cf: T. Masaoka et al, Bone Marrow Transplantation, Vol. 3, 121-127, 1988). Therefore, human M-CSFs have been highly expected to be used as a drug.
With respect to the safeness and scarce side effects in dosage of hM-CSFs have been clinically confirmed (cf: K. Motoyoshi et al, Immunobiology, Vol. 172, 205-212, 1986).
It has been known that monocyte-macrophage lineage is significantly related with hyperlipemia and arteriosclerosis.